Transplant Tolerance

Unlike other parts of the body, the eye doesn't swell up in response to injury or infection. Swelling can damage the eye's fragile tissues, so a safety mechanism in the eye prevents that from happening. Now, researchers are studying how the eye does this. In this Science Update, you'll hear why that knowledge could someday help organ transplant patients.

Transcript

How the eye teaches tolerance. I'm Bob Hirshon and this is Science Update.

Organ transplant patients take powerful drugs to suppress their immune system in order to prevent rejection. But their weakened immune system puts them at risk of developing deadly infections.

Now, Emory University School of Medicine ophthalmologist Judith Kapp may have found an alternative to these dangerous drugs—inside the human eye.

Kapp: It's been known for fifty years that the eye is a special spot in the body. The immune response there usually is a very blunted response.

As a result, the eye doesn't reject transplanted corneas and lenses. In a recent study with mice, Kapp and a colleague found the eye tolerates these implants, thanks to immune cells called gamma-delta-T cells. And once these T-cells are activated by a particular infectious agent, they prevent an immune response to that same agent in other parts of the body.

Kapp: We might someday envision that we would pre-treat a particular patient who is going to be a recipient, in a way to make them tolerant to the donor tissue.

So instead of a lifetime of drugs after the transplant, patients could get an injection to prepare for the new organ beforehand. For the American Association for the Advancement of Science, I'm Bob Hirshon.

Making Sense of the Research

Although many people are alive today only because of organ transplants, the quality of life for these patients could be much improved. For one thing, they face the risk of organ rejection, even long after the transplant. On the other hand, the immune-suppressing drugs they take to reduce the risk of rejection are powerful and debilitating.

That's why doctors are so eager to find new ways to control organ rejection. The eye's strategy is especially attractive because it's antigen-specific. An antigen is any foreign substance that the body's immune system might react to. The gamma-delta-T-cells in the eye can suppress the immune system's response to just one particular antigen. So in theory, by enlisting gamma-delta-T-cells, you could "teach" the body not to attack cells from a transplanted liver—without weakening its response to other antigens, like viruses and bacteria.

The study completed by Kapp (actually an immunologist in the ophthamology department) and her colleagues lays the groundwork for pursuing this goal. They've shown that gamma-delta-T-cells are, in fact, the key to the eye's special immune-suppressing process. In their experiment, they compared genetically engineered mice that couldn't produce gamma-delta-T-cells with normal mice that could. Only the normal mice were able to suppress their immune response to an antigen introduced into the eye.

Now, Kapp's team is trying to get a clearer picture of how this works. In new experiments already in progress, they've genetically altered gamma-delta-T-cells so they're easy to track in a mouse's body. And they're following the path these T-cells take, paying close attention to what other cells they interact with and what kinds of chemicals they produce. Only by fully understanding how the process works in the eye will they be able to attempt to transfer it to other parts of the body.

The eye isn't the only organ that's drawn attention because of its unique biomedical properties. For example, scientists have long been interested in how the liver regenerates itself, unlike other organs. And many researchers are intrigued by the properties of embryonic cells (immature cells from human embryos), because they have the potential to develop into many different kinds of tissue. If scientists could figure out how to transfer either of these properties to adult cells, it could revolutionize the way we treat and repair damaged organs.

Now try and answer these questions:

Why is the eye interesting to medical researchers?

What are gamma-delta-T-cells? Why are they important?

Suppose gamma-delta-T-cells could be used to prevent rejection in organ transplant recipients. Name some of the advantages this technique might offer, compared to the procedures used today.

What obstacles might stand in the way of adapting this technique for transplant patients?

Besides rejection by the immune system, can you name some of the problems that make organ transplantation difficult?